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INTRODUCTION

INTRODUCTION. Cancer pharmacology has changed dramatically as curative treatments have been identified for many previously fatal malignancies such as testicular cancer, lymphomas, and leukemia. Adjuvant chemotherapy and hormonal therapy can extend life and prevent disease recurrence following surgical resection of localized breast, colorectal, and lung cancers. Chemotherapy is also employed as part of the multimodal treatment of locally advanced head and neck, breast, lung, and esophageal cancers, soft-tissue sarcomas, and pediatric solid tumors, thereby allowing for more limited surgery and even cure in these formerly incurable cases. Colony-stimulating factors restore bone marrow function and expand the utility of high-dose chemotherapy. Chemotherapeutic drugs are increasingly used in nonmalignant diseases: cytotoxic antitumor agents have become standard in treating autoimmune diseases, including rheumatoid arthritis (methotrexate and cyclophosphamide), Crohn disease (6-mercaptopurine), organ transplantation (methotrexate and azathioprine), sickle cell anemia (hydroxyurea), and psoriasis (methotrexate). Despite these therapeutic successes, few categories of medication have a narrower therapeutic index and greater potential for causing harmful effects than the cytotoxic antineoplastic drugs. A thorough understanding of their pharmacology, including drug interactions and clinical pharmacokinetics, is essential for their safe and effective use in humans.

The compounds used in the chemotherapy of neoplastic disease are quite varied in structure and mechanism of action, including alkylating agents; antimetabolite analogs of folic acid, pyrimidine, and purine; natural products; hormones and hormone antagonists; and a variety of agents directed at specific molecular targets. Tables 60-1, 60-2, 60-3, 60-4 and 60-5 summarize of the main classes and examples of these drugs. Figure 60-1 depicts the cellular targets of chemotherapeutic agents.